CSF2RB mutation-related hereditary pulmonary alveolar proteinosis: the "long and winding road" into adulthood

Spyros A Papiris^{1

2}, Camille Louvrier^{3

4

2}, Aurélie Fabre^{5

6}, Loukas Kaklamanis⁷, Iraklis Tsangaris⁸, Frantzeska Frantzeskaki⁸, Ilias E Dimeas⁹, Marie-Pierre Debray^{10

11}, Foteini Karakontaki¹², Maria Kallieri¹, Lykourgos Kolilekas¹³, Zoe Daniil⁹, Alexandra Giatromanolaki¹⁴, Caroline Kannengiesser^{15

16}, Raphael Borie¹⁷, Nadia Nathan¹⁸, Matthias Griese¹⁹, Effrosyni D Manali¹

Affiliations

¹ 2nd Pulmonary Department, General University Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, Athens, Greece.
² These authors contributed equally to this work.
³ Sorbonne Université, Inserm, Laboratory of Childhood Genetic Disorders, UMR S933, Hôpital Armand-Trousseau, Paris, France.
⁴ Département de Génétique Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, Paris, France.
⁵ Department of Pathology, St Vincent's University Hospital, Dublin, Ireland.
⁶ School of Medicine, University College Dublin, Dublin, Ireland.
⁷ Heart Failure and Transplant Units, Onassis Cardiac Surgery Center, Athens, Greece.
⁸ 2nd Department of Critical Care Medicine, General University Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁹ Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Biopolis, Larissa, Greece.
¹⁰ Service de Radiologie, Hôpital Bichat, APHP, Paris, France.
¹¹ INSERM, Unité 1152, Université de Paris, Paris, France.
¹² 1st Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, "Sotiria" Chest Hospital, Athens, Greece.
¹³ 7th Pulmonary Department, Athens Chest Hospital "Sotiria", Athens, Greece.
¹⁴ Department of Pathology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
¹⁵ Département de Génétique, APHP Hôpital Bichat, Université de Paris, Paris, France.
¹⁶ INSERM UMR 1152, Université de Paris, Paris, France.
¹⁷ Service de Pneumologie A, INSERM UMR_1152, Centre de Référence des Maladies Pulmonaires Rares, FHU APOLLO, APHP Hôpital Bichat, Sorbonne Université, Paris, France.
¹⁸ Pediatric Pulmonology Department and Reference Centre for Rare Lung Diseases RespiRare, INSERM UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Sorbonne University and APHP, Paris, France.
¹⁹ Department of Pediatric Pneumology, Dr von Hauner Children's Hospital, Ludwig-Maximilians-University, German Center for Lung Research, Munich, Germany.

PMID: 38111540
PMCID: PMC10726220
DOI: 10.1183/23120541.00703-2023

CSF2RB mutation-related hereditary pulmonary alveolar proteinosis: the "long and winding road" into adulthood

Spyros A Papiris et al. ERJ Open Res. 2023.

. 2023 Dec 18;9(6):00703-2023.

doi: 10.1183/23120541.00703-2023. eCollection 2023 Nov.

Authors

Affiliations

¹ 2nd Pulmonary Department, General University Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, Athens, Greece.
² These authors contributed equally to this work.
³ Sorbonne Université, Inserm, Laboratory of Childhood Genetic Disorders, UMR S933, Hôpital Armand-Trousseau, Paris, France.
⁴ Département de Génétique Médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, Paris, France.
⁵ Department of Pathology, St Vincent's University Hospital, Dublin, Ireland.
⁶ School of Medicine, University College Dublin, Dublin, Ireland.
⁷ Heart Failure and Transplant Units, Onassis Cardiac Surgery Center, Athens, Greece.
⁸ 2nd Department of Critical Care Medicine, General University Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁹ Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Biopolis, Larissa, Greece.
¹⁰ Service de Radiologie, Hôpital Bichat, APHP, Paris, France.
¹¹ INSERM, Unité 1152, Université de Paris, Paris, France.
¹² 1st Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, "Sotiria" Chest Hospital, Athens, Greece.
¹³ 7th Pulmonary Department, Athens Chest Hospital "Sotiria", Athens, Greece.
¹⁴ Department of Pathology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
¹⁵ Département de Génétique, APHP Hôpital Bichat, Université de Paris, Paris, France.
¹⁶ INSERM UMR 1152, Université de Paris, Paris, France.
¹⁷ Service de Pneumologie A, INSERM UMR_1152, Centre de Référence des Maladies Pulmonaires Rares, FHU APOLLO, APHP Hôpital Bichat, Sorbonne Université, Paris, France.
¹⁸ Pediatric Pulmonology Department and Reference Centre for Rare Lung Diseases RespiRare, INSERM UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Sorbonne University and APHP, Paris, France.
¹⁹ Department of Pediatric Pneumology, Dr von Hauner Children's Hospital, Ludwig-Maximilians-University, German Center for Lung Research, Munich, Germany.

PMID: 38111540
PMCID: PMC10726220
DOI: 10.1183/23120541.00703-2023

Abstract

Genetic analysis pre-lung transplantation diagnosed a case of hereditary pulmonary alveolar proteinosis (PAP) complicated by fibrosis in adulthood. The need for genetic testing in GM-CSF autoantibody negative and unclassifiable PAP is highlighted. https://bit.ly/3QcsYwM.

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Conflict of interest statement

Conflict of interest: S.A. Papiris reports grants or contracts as the Savara Impala 2 Trial Primary Investigator, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim, DEMO, Hoffman la Roche and Elpen, outside the submitted work; and support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work. Conflict of interest: R. Borie reports receiving consulting fees from Boehringer Ingelheim, Sanofi and Ferrer, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim, Sanofi and Ferrer, outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work; and participation on a data safety monitoring or advisory board for Savara, outside the submitted work. Conflict of interest: N. Nathan reports grants or contracts from the Orphan Disease Center, Genetic Basis of Neuroendocrine Cell Hyperplasia of Infancy (principal investigator (PI)), French Research and Innovation Grant 2023 (CORTICO-NEHI; PI) and Chancellerie des universités (PI), outside the submitted work; participation on a data safety monitoring or advisory board for Research and Innovation AP-HP, France (member), outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for a Clinical Research Collaboration on chILDEU of the European Respiratory Society (2022–present). Conflict of interest: M. Griese reports Boehringer Ingelheim support for an adjudication board, outside the submitted work. Conflict of interest: E.D. Manali reports grants or contracts as a Savara Impala 2 Trial Subinvestigator, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim, CSL Behring, Hoffman la Roche and Elpen, outside the submitted work; and support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose.

Figures

**FIGURE 1**
a) Histological features of lung video-assisted thoracoscopic surgery biopsy (2004, at the age of 29 years; 18 years prior to transplantation) showing pulmonary alveolar proteinosis (PAP) and chronic lymphocytic inflammation associated with interstitial cholesterol clefts granulomas and cystically dilated subpleural alveolar spaces with collagenous fibrosis; scale bar=500 μm. b) Chest computed tomography scan performed in 2013 at the age of 38 years shows extensive patchily distributed ground-glass opacities and nodular consolidations with some subpleural sparing (arrow). A few cysts are present, but there are no signs of distortion; pure crazy-paving pattern is not disclosed probably due to the hereditary nature of the development of the disease and the very long evolution in this patient. c) 9 years later, at the age of 47 years, ground-glass opacities and consolidations have dramatically decreased, replaced by numerous clustered cysts. d) Histological features of the explanted lungs showing mixed PAP and usual interstitial pneumonia (UIP) patterns with honeycombing and fibrosis on the explanted lung; note the clear demarcation between the PAP areas and UIP areas with minimal overlap (haematoxylin and eosin stain); scale bar=1000 μm.

See this image and copyright information in PMC

References

1. Trapnell BC, Nakata K, Bonella F, et al. . Pulmonary alveolar proteinosis. Nat Rev Dis Primers 2019; 5: 16. doi:10.1038/s41572-019-0066-3 - DOI - PubMed
1. Griese M. Pulmonary alveolar proteinosis: a comprehensive clinical perspective. Pediatrics 2017; 140: e20170610. doi:10.1542/peds.2017-0610 - DOI - PubMed
1. Suzuki T, Maranda B, Sakagami T, et al. . Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations. Eur Respir J 2011; 37: 201–204. doi:10.1183/09031936.00090610 - DOI - PubMed
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CSF2RB mutation-related hereditary pulmonary alveolar proteinosis: the "long and winding road" into adulthood

Affiliations

CSF2RB mutation-related hereditary pulmonary alveolar proteinosis: the "long and winding road" into adulthood

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Research Materials